The overall objective of this integrated group of research studies is a more comprehensive understanding of the pathophysiology of unipolar and bipolar affective disorders, particularly with regard to the complex interrelationships among clinical phenomenology, diagnosis, biological variables, and pharmacologic response. The studies are both cross-sectional and longitudinal; drug trials are double-blind. This past year, a new program has been initiated emphasizing a brief pre-treatment inpatient evaluation of patients with a variety of endogenous and non-endogenous depressive syndromes, followed by outpatient treatment. Meanwhile, longitudinal inpatient studies of endogenous depression, mania, and rapid-cycling bipolar illness continue. Major projects include the study of circadian rhythms, neuroendocrine substances and monoamine neurotransmitters and their metabolites, both during untreated affective episodes and following specific treatment. The primary treatment modalities include 1) environmental manipulations, such as sleep deprivation or sleep shifts, 2) tricyclic antidepressants showing specificity for given neurotransmitter systems, and 3) electroconvulsive therapy (ECT).